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Original Investigation
September 14, 2020

Association of Pregnancy With the Onset of Clinically Isolated Syndrome

Author Affiliations
  • 1Department of Neurology, Royal Melbourne Hospital, Melbourne, Victoria, Australia
  • 2CORe, Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia
  • 3Department of Neurology and Center of Clinical Neuroscience, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic
  • 4Department of Health Sciences (DISSAL), Biostatistics Unit, University of Genoa, Genoa, Italy
  • 5Department of Neurology, John Hunter Hospital, Newcastle, New South Wales, Australia
  • 6School of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales, Australia
  • 7Centre for Brain and Mental Health, Hunter Medical Research Institute, Newcastle, New South Wales, Australia
  • 8Department of Neurology, Alfred Hospital, Melbourne, Victoria, Australia
  • 9Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia
  • 10Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Victoria, Australia
JAMA Neurol. 2020;77(12):1496-1503. doi:10.1001/jamaneurol.2020.3324
Key Points

Question  Do pregnancies and childbirths delay the onset of clinically isolated syndrome (CIS)?

Findings  In this multicenter cohort study of 2557 women with CIS, women with previous pregnancies and childbirths had a later onset of CIS compared with women without pregnancies and childbirths. A higher number of pregnancies and childbirths was not associated with later CIS onset.

Meaning  Findings of this study suggest that future research is needed to explore the mechanisms underpinning the association between pregnancy and timing of the first presentation of multiple sclerosis.


Importance  Multiple sclerosis (MS) is usually diagnosed in women during their childbearing years. Currently, no consensus exists on whether pregnancy can delay the first episode of demyelination or clinically isolated syndrome (CIS).

Objective  To investigate the association of pregnancy with time to CIS onset.

Design, Setting, and Participants  This multicenter cohort study collected reproductive history (duration of each pregnancy, date of delivery, length of breastfeeding) on all participants between September 1, 2016, and June 25, 2019. Adult women being treated at the MS outpatient clinics of 4 tertiary hospitals in 2 countries (Charles University and General University Hospital in Prague, Czech Republic; Royal Melbourne Hospital in Melbourne, Australia; Alfred Hospital in Melbourne, Australia; and John Hunter Hospital in Newcastle, Australia) were recruited to participate in the study. Preexisting data (date of CIS onset, date of birth, sex, date of clinical onset, and Expanded Disability Status Scale result) were collected from MSBase, an international registry of long-term prospectively collected data on patients with MS. Data analyses were performed from June 1, 2019, to February 3, 2020.

Exposures  Gravida (defined as any pregnancy, including pregnancy that ended in miscarriage and induced abortion) and parity (defined as childbirth after gestational age of more than 20 weeks, including livebirth and stillbirth) before CIS onset.

Main Outcomes and Measures  Time to CIS onset. The following were assessed: (1) whether women with previous pregnancies and childbirths had a delayed onset of CIS compared with those who had never been pregnant and those who had never given birth, and (2) whether a dose response existed, whereby a higher number of gravidity and parity was associated with a later onset of CIS.

Results  Of the 2557 women included in the study, the mean (SD) age at CIS onset was 31.5 (9.7) years. Of these women, before CIS onset, 1188 (46%) had at least 1 pregnancy and 1100 (43%) had at least 1 childbirth. The mean (SD) age at first pregnancy was 23.3 (4.5) years and at first childbirth was 23.8 (4.5) years. Women with previous pregnancies and childbirths had a later onset of CIS compared with those who had never been pregnant (HR, 0.68; 95% CI, 0.62-0.75; P < .001), with a median delay of 3.3 (95% CI, 2.5-4.1) years. Women who had given birth also had a later CIS onset compared with women who had never given birth (HR 0.68; 95% CI, 0.61-0.75; P < .001), with a similar median delay of 3.4 (95% CI, 1.6-5.2) years. A higher gravidity and parity number was not associated with delay in CIS onset.

Conclusions and Relevance  This study suggests an association between previous pregnancies and childbirths and timing of CIS onset, but having more pregnancies or childbirths did not appear to be associated with a later CIS onset. Further studies are needed to help explain the mechanisms behind the associations between pregnancy and onset of multiple sclerosis.

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